PARTICIPATION OF GABA(A)-MEDIATED INHIBITION IN ICTALLIKE DISCHARGES IN THE RAT ENTORHINAL CORTEX

Participation of GABA,mediated inhibition In ictallike discharges in t he rat entorhinal cortex. J. Neurophysiol. 79: 352-360, 1998. The spon taneous, synchronous activity induced by 4-aminopyridine (4AP, 50 mu M ) in the adult rat entorhinal cortex was analyzed with simultaneous he ld potential and intracellular recordings in an in vitro slice prepara tion. Four-AP induced isolated negative-going field potentials (interv al of occurrence = 27.6 +/- 9.9) (SD) s;( a = 27 slices) that correspo nded to intracellular long-lasting depolarizations (LLDs), and ictalli ke epileptiform discharges (interval of occurrence = 10.4 +/- 5.7 min; n = 27 slices) that were initiated by the negative field potentials. LLDs recorded with K-acetate-filled microelectrodes triggered few acti on potentials of variable amplitude and had a duration of 1.7 +/- 0.8 s (n = 26 neurons), a peak amplitude of 11.8 +/- 5.0 mV (a = 26 neuron s) and a reversal potential of -66.2 +/- 3.9 mV(n = 17 neurons). The i ctal discharges studied with K-acetate microelectrodes consisted of pr olonged depolarizations (duration = 72.9 +/- 44.3 s; peak amplitude = 29.2 +/- 11.4 mV; n = 25 neurons) with action-potential firing during both the tonic and the clonic phase. These depolarizations had a rever sal potential of -45.3 +/- 3.8 mV (n = 4 neurons). Intracellular Cl-di ffusion from KCl-filled microelectrodes made both LLDs and ictal depol arizations increase in amplitude (30.5 +/- 8.2 mV, n = 8 and 41.8 +/- 9.8 mV, n = 6 neurons, respectively). LLDs recorded with KCI and -(tri methyl-amino)N-(2,6-dimethylphenyl)-acetamide (QX-314) microelectrodes reached an amplitude of 36.3 +/- 5.2 mV, lasted 12.5 +/- 6.5 s, and h ad a reversal potential of -31.3 +/- 2.5 mV (a = 4 neurons); under the se recording procedures the ictal discharge amplitude was 41.5 +/- 5.0 mV and the reversal potential -24.0 +/- 7.0 mV (n = 4 neurons). The h i-methyl-D-aspartate (NMDA) receptor antagonist -(2-carboxy-piperazine -4-yl)-pro-pyl-l-phosphonate (10 mu M, n = 5 neurons) alone or concomi tant with the nonNMDA receptor antagonist 6-cyano-7-nitro-quinoxaline- 2,3-dione (10 mu M, n = 4 neurons) abolished ictal discharges,without influencing LLDs. LLDs were blocked by the gamma-aminobutyric acid-A ( GABA(A)) receptor antagonist bicuculline methiodide (BMI, 10 mu M, a = 6 neurons) or the mu-opioid receptor agonist (D-Ala2-N-Me-Phe, Glyol) enkephalin (DAGO, 10 mu M, n = 2 neurons). Application of BMI (n = 4 neurons) or DAGO (n = 2 neurons) to control the medium abolished LLDs and ictal discharges but disclosed a novel type of epileptiform depola rization that lasted 3.5 +/- 1.2 s and occurred every 5.2 +/- 2.6 a (n = 6 neurons). Our data indicate that 4AP induces in the rat entorhina l cortex a synchronous, GABA-mediated potential that is instrumental i n initiating NMDA-dependent, ictal discharges. Moreover we present evi dence for an active role played by GABAA-mediated potentials in the ma intenance and termination of these prolonged epileptiform events.